title: Polymorphism of the RAGE affects the serum inflammatory levels and risk of ischemic stroke in a Chinese population.
abstract: BACKGROUND
  Increasing evidence shows that inflammation plays an important role in the occurrence and progression of acute ischemic stroke. The receptor for advanced glycation end products (RAGE) has been documented to involve in the pathogenic mechanisms of a variety of neurological diseases, including ischemic stroke (IS). However, the impact of RAGE gene polymorphisms on the susceptibility to IS has not been reported. We thus explored the association between RAGE gene polymorphisms and the susceptibility to IS.
  
  
  METHODS
  A total of 384 patients with IS and 425 healthy controls were enrolled in this study. Three genetic polymorphisms of RAGE gene (82G/S, -429T/C and -374T/A) were determined. The serum levels of soluble RAGE (sRAGE), intetleukin-6 (IL-6), high sensitivity-C reaction protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) were detected.
  
  
  RESULTS
  Among the studied polymorphisms, only the polymorphism at 82G/S of RAGE gene was associated with the risk for ischemic stroke irrespective of the stroke subtypes. The 82S/S homozygote carriers had a significantly increased risk for ischemic stroke [adjusted odds ratio (OR): 2.297; p<0.001]. The haplotype analyses showed that the C-429S82T-374 and T-429S82A-374 had higher risk to develop IS (OR=1.864 and 1.931, respectively, all p<0.01), while the C-429G82T-374 showed a protective effect against IS susceptibility (OR=0.568, p=0.001). In addition, the 82S/S homozygote carriers had a higher inflammatory level compared with 82G/S and 82G/G genotypes, indicated by lower serum sRAGE level, higher serum IL-6, hs-CRP and PAI-1 levels. The polymorphisms at -374 and -429 loci did not influence the stroke risk and the above mentioned inflammation cytokines.
  
  
  CONCLUSIONS
  Our results showed a close correlation between the 82G/S polymorphism and the susceptibility to IS, suggesting the 82G/S polymorphism may be used as a genetic marker for the prediction of stroke occurrence in high risk subjects.
authors.affiliation: Department of Neurosurgery, Fuzhou General Hospital of Xiamen University, Fujian, China.
authors.forename: XiaoPing
authors.initials: X
authors.lastname: Cui
authors.forename: Hongjie
authors.initials: H
authors.lastname: Chen
authors.forename: Xuwei
authors.initials: X
authors.lastname: Hou
authors.forename: ShouSen
authors.initials: S
authors.lastname: Wang
authors.forename: Shoba
authors.initials: S
authors.lastname: Jayaram
authors.forename: ZhaoCong
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000368:Aged; D044466:Asian People; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D020521:Stroke / Q000097:blood / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C051321:SERPINE1 protein, human; D002097:C-Reactive Protein